The present invention relates to drugs and, particularly, to anticancer agents. More particularly, the present invention relates to an anticancer agents containing, as an active ingredient, at least one compound selected from the group consisting of xcfx89-hydroxy fatty acids and salts or esters thereof, hydroxy oxo-fatty acids and salts or esters thereof, lactones, macrocyclic ketones, and macrocyclic diesters.
Many anticancer agents, including bleomycin, Pepleostatin, and Mitomycin (registered trade name), have been developed. However, these agents have strong side effects, such as cytotoxicity, and moreover, in order to exert a satisfactory action of inhibiting metastasis, they must be administered in large quantities, which may prove to be fatal.
Under the circumstances, attention has been given to the development of compounds having decreased side effects. As a result, antitumor agents containing carbon, hydrogen, and oxygen only have been proposed, for example, antitumor agents containing unsaturated fatty acids, such as linoleic acid and oleic acid (disclosed in JP-A-Syouwa62-12716, etc.), ketol-type unsaturated fatty acids (disclosed in JP-A-Heisei5-279252), hydroxylinoleic acid (disclosed in JP-A-Heisei7-291862), and 10-oxo-11(E)-octadecen-13-olide, which is a new macrolide compound (disclosed in JP-A-Heisei6-220037).
However, in these antitumor agents, merely the action of killing tumors is demonstrated, and since known antitumor agents use natural extracts as raw materials, in order to ensure purities necessary for antitumor agents, extremely complex purifying processes must be performed, resulting in production difficulty on an industrial scale.
Accordingly, it is an object of the present invention to provide an anticancer agents which is easily produced, which has an activity of inhibiting cancer metastasis in addition to an activity of killing cancer, and which also has decreased side effects.
xe2x80x9cAnticancer agentsxe2x80x9d in the present invention mean agents which are used for the purpose of killing cancer, inhibiting the metastasis of cancer, preventing the recurrence of cancer, preventing cancer, or the like.
The present inventors have carried out thorough research on substances which can be mass-produced in high purities on an industrial scale, which are highly safe, and which exhibit satisfactory absorption into cells, and found that xcfx89-hydroxy fatty acids and salts or esters thereof, hydroxy oxo-fatty acids and salts or esters thereof, lactones, macrocyclic ketones, and macrocyclic diesters having specific chemical structures are anticancer agents which have significantly high activities of killing cancer and inhibiting the metastasis of cancer, and thus the present invention has been achieved.
In one aspect of the present invention, the anticancer agents contain, as an active ingredient, at least one compound selected from the group consisting of:
an xcfx89-hydroxy fatty acid represented by general formula (1) or a salt or ester thereof:
HOxe2x80x94R1xe2x80x94COOHxe2x80x83xe2x80x83(1)
xe2x80x83wherein R1 is a straight carbon chain having 10 to 25 carbon atoms, with no or one double bond, where an alkyl or alkylene group having 1 to 4 carbon atoms or a hydroxyl group may be linked to any position as a side chain;
a hydroxy oxo-fatty acid represented by general formula (2) or a salt or ester thereof:
R2xe2x80x94COOHxe2x80x83xe2x80x83(2)
xe2x80x83wherein R2 is a saturated straight carbon chain having 9 to 25 carbon atoms, with at least one carbonyl group and at least one hydroxyl group, where an alkyl or alkylene group having 1 to 4 carbon atoms may be linked to any position as a side chain;
a lactone represented by general formula (3): 
xe2x80x83wherein R3 is a carbon chain having 2 to 24 carbon atoms which is saturated or unsaturated by including at least one carbon-carbon double bond in any position, or a carbon chain having 8 to 24 carbon atoms with at least one oxygen atom in any position which is saturated or unsaturated by including at least one carbon-carbon double bond in any position, where an alkyl or alkylene group having 1 to 4 carbon atoms may be linked to any position as a side chain; R4 is hydrogen, a hydroxyl group, or a carbon chain having 1 to 30 carbon atoms which is saturated or unsaturated by including at least one carbon-carbon double bond in any position, where an alkyl or alkylene group having 1 to 4 carbon atoms may be linked to any position; and the dashed line represents a single bond or a double bond;
a macrocyclic ketone represented by general formula (4): 
xe2x80x83wherein R5 is hydrogen or an alkyl or alkylene group having 1 to 4 carbon atoms; R6 is a carbon chain having 7 to 17 carbon atoms which is saturated or unsaturated by including at least one carbon-carbon double bond in any position, where an alkyl or alkylene group having 1 to 4 carbon atoms may be linked to any position as a side chain; R7 is hydrogen or an alkyl group or an alkylene group having 1 to 4 carbon atoms; and the dashed line represents a single bond or a double bond; and
a macrocyclic diester represented by general formula (5) 
xe2x80x83wherein R8 is a carbon chain having 2 to 10 carbon atoms which is saturated or unsaturated by including at least one carbon-carbon double bond in any position, where an alkyl or alkylene group having 1 to 4 carbon atoms may be linked to any position; and R9 is a carbon chain having 8 to 20 carbon atoms which is saturated or unsaturated by including at least one carbon-carbon double bond in any position.
That is, as described above, the anticancer agents of the present invention contains, as an active ingredient, at least one compound selected from the group consisting of xcfx89-hydroxy fatty acids and salts or esters thereof, hydroxy oxo-fatty acids and salts or esters thereof, lactones, macrocyclic ketones, and macrocyclic diesters. These compounds used in the present invention can be combined with the existing anticancer agents.
In the meantime, although various methods for making xcfx89-hydroxy fatty acids are known, since many types of impurities are produced due to various side reactions in all of the methods, in order to highly purify the resultant xcfx89-hydroxy fatty acids, complex purification processes must be performed. However, as a result of thorough research carried out by the present inventors, it has been found that by opening the ring of the lactone of the present invention by hydrolysis, an xcfx89-hydroxy fatty acid can be obtained in high purities in a significantly simple way, and thus the present invention has been achieved.
All of the xcfx89-hydroxy fatty acids and salts or esters thereof, hydroxy oxo-fatty acids and salts or esters thereof, lactones, macrocyclic ketones, and macrocyclic diesters used in the present invention, as compounds themselves, include known compounds, and have been industrially mass-produced mainly as raw materials for perfume compounds and as perfume compounds.
That is, with respect to the compounds used in the present invention, the industrial production methods therefor have been established and they have previously been used for fragrance materials rather than anticancer agents, i.e., they are readily available compounds with high purities.
As the xcfx89-hydroxy fatty acid or a salt or ester thereof used in the present invention, any compound represented by the following general formula (1) may be used:
HOxe2x80x94R1xe2x80x94COOHxe2x80x83xe2x80x83(1)
wherein R1 is a straight carbon chain having 10 to 25 carbon atoms, with no or one double bond, where an alkyl or alkylene group having 1 to 4 carbon atoms or a hydroxyl group may be linked to any position as a side chain. Preferably, R1 is a straight carbon chain which is saturated or which has one double bond, in which a hydroxyl group is linked to the xcfx89 position. Preferred examples of xcfx89-hydroxy fatty acids include 12-hydroxydodecanoic acid, 14-hydroxytetradodecanoic acid, 15-hydroxypentadecanoic acid, 16-hydroxyhexadecanoic acid, 17-hydroxyheptadecanoic acid, 18-hydroxyoctadecanoic acid, 15-hydroxy-11-pentadecenoic acid, 15-hydroxy-12-pentadecenoic acid, 16-hydroxy-9-hexadecenoic acid, and 16-hydroxy-7-hexadecenoic acid. Preferred examples of esters include ethyl esters and n-propyl esters of these xcfx89-hydroxy fatty acids.
These xcfx89-hydroxy fatty acids may be produced by any known method. More preferably, in order to easily obtain high-purity products, the ring of a lactone represented by the following general formula (3) is opened, for example, by alkaline hydrolysis, and then acid treatment is performed: 
wherein R3 is a carbon chain having 8 to 24 carbon atoms which is saturated or unsaturated by including one or two carbon-carbon double bonds in any positions, where an alkyl or alkylene group having 1 to 4 carbon atoms may be linked to any position as a side chain; R4 is hydrogen or an alkyl or alkylene group having 1 to 4 carbon atoms; and the dashed line represents a single bond or a double bond. Additionally, with respect to the lactones used as the raw materials, the industrial production methods have been established, and they have already been mass-produced as fragrance materials. Therefore, high-purity products can be more easily obtained by using them.
As the hydroxy oxo-fatty acid or a salt or ester thereof used in the present invention, any compound represented by the following general formula (2) may be used:
R2xe2x80x94COOHxe2x80x83xe2x80x83(2)
wherein R2 is a saturated straight carbon chain having 9 to 25 carbon atoms, with at least one carbonyl group and at least one hydroxyl group, where an alkyl or alkylene group having 1 to 4 carbon atoms may be linked to any position as a side chain. Preferably, the hydroxyl group is located at the xcfx89 position of R2 in the formula because the industrial production method therefor has been established. Preferably, the number of carbonyl groups is one, and the carbonyl group is located at the xcfx89-3 position. More preferred is any one of 11-hydroxy-8-oxoundecanoic acid, 12-hydroxy-9-oxododecanoic acid, 13-hydroxy-10-oxotridecanoic acid, 14-hydroxy-11-oxotetradecanoic acid, 15-hydroxy-12-oxopentadecanoic acid, 16-hydroxy-13-oxohexadecanoic acid, 17-hydroxy-14-oxoheptadecanoic acid, 18-hydroxy-15-oxooctadecanoic acid, 19-hydroxy-16-oxononadecanoic acid, 20-hydroxy-17-oxoeicosanoic acid, and 21-hydroxy-18-oxoheneicosanoic acid. More preferred examples of esters include ethyl esters and n-propyl esters of these hydroxy oxo-fatty acids.
As the method for producing the hydroxy oxo-fatty acids, any appropriate known method may be used. For example, International Patent Application Publication No. W097/06156 discloses that an xcfx89-hydroxy-(xcfx89-3)-keto-fatty acid is produced by condensing xcex3-butyrolactone with an ester of dicarboxylic acid, followed by hydrolysis and decarboxylation. Japanese Patent No. 2595094 also discloses a method in which an xcex1-(xcfx89-cyanoalkanoyl)-xcex3-butyrolactone is used as a raw material, and hydrolysis and decarboxylation are performed to produce an xcfx89-hydroxy-(xcfx89-3)-keto-fatty acid.
The xcfx89-hydroxy fatty acids represented by the general formula (1) described above, the salts or a salt thereof can be easily obtained as high-purity products either by hydrolyzing lactones using acids or alkalis, followed by recrystallization, or by further performing acidification after hydrolysis in the case of alkaline hydrolysis, followed by recrystallization or purification by distillation.
In the present invention, although the acid used for hydrolysis of the lactone described above is not particularly limited as long as the lactone can be hydrolyzed, at least one mineral acid, such as hydrochloric acid, sulfuric acid, phosphoric acid, or nitric acid is preferably used.
Although the alkali used for hydrolysis of the lactone described above is not particularly limited as long as the lactone can be hydrolyzed, lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, or the like is preferably used, and two or more of these may be used in combination.
In the hydrolysis in the present invention, the equivalent weight of the acid or alkali used is desirably 0.7 or more relative to the lactone, preferably 1 to 10, and more preferably 1 to 3. The solvent used in the hydrolysis is not particularly limited as long as it is a mixed solvent with water or a water-soluble solvent. Examples of water-soluble solvents include methanol, ethanol, propanol, 2-propanol, acetone, tetrahydrofuran, ethylene glycol, ethylene glycol monomethyl ether, ethylene glycol dimethyl ether, and 1,4-dioxane, and a mixed solvent including at least one of these in a certain ratio may be used.
When alkali hydrolysis is performed, by recrystallizing the solution of the alkali salt obtained under the conditions described above, an xcfx89-hydroxy fatty acid salt can be obtained in high purities. Furthermore, by subjecting the xcfx89-hydroxy fatty acid salt to acid treatment after the hydrolysis, an xcfx89-hydroxy fatty acid may be obtained. Although the acid used in the acid treatment is not particularly limited as long as it neutralizes and then acidifies the alkali salt in which the ring has been opened by the hydrolysis, at least one mineral acid, such as hydrochloric acid, sulfuric acid, phosphoric acid, or nitric acid is preferably used. After the acid treatment is performed, either by recrystallization using a recrystallizing solvent, such as ethyl acetate, toluene, hexane, or ether, or by distillation, a high-purity xcfx89-hydroxy fatty acid can be obtained.
As the lactone used in the present invention, any compound represented by the following general formula (3) may be used: 
wherein R3 is a carbon chain having 2 to 24 carbon atoms which is saturated or unsaturated by including at least one carbon-carbon double bond in any position, or a carbon chain having 8 to 24 carbon atoms, with at least one oxygen atom in any position, which is saturated or unsaturated by including at least one carbon-carbon double bond in any position, where an alkyl or alkylene group having 1 to 4 carbon atoms may be linked to any position as a side chain; R4 is hydrogen, a hydroxyl group, or a carbon chain having 1 to 30 carbon atoms which is saturated or unsaturated by including at least one carbon-carbon double bond in any position, where an alkyl or alkylene group having 1 to 4 carbon atoms may be linked to any position; and the dashed line represents a single bond or a double bond. The industrial production methods for these compounds have been established, and the lactones used in the present invention may be produced by the known methods. However, these compounds have already been mass-produced as fragrance materials and high-purity products are easily obtainable. Most preferred examples of lactones include 12-dodecanolide, 15-pentadecanolide, 16-hexadecanolide, 11-pentadecen-15-olide, 12-pentadecen-15-olide, 7-hexadecen-16-olide, 9-hexadecen-16-olide, 10-oxahexadecanolide, 11-oxahexadecanolide, 12-oxahexadecanolide, 4-butanolide, 12-oxahexadecen-16-olide, 4-pentanolide, 4-hexanolide, 4-heptanolide, 4-octanolide, 4-nonanolide, 4-decanolide, 4-undecanolide, 4-dodecanolide, 4-tridecanolide, 4-tetradecanolide, 4-pentadecanolide, 4-hexadecanolide, 4-heptadecanolide, 4-octadecanolide, 4-nonadecanolide, 4-icosanolide, 4-methyl-4-decanolide, 5-hexanolide, 5-heptanolide, 5-octanolide, 5-nonanolide, 5-decanolide, 5-undecanolide, 5-dodecanolide, 5-tridecanolide, 5-tetradecanolide, 5-pentadecanolide, 5-hexadecanolide, 5-heptadecanolide, 5-octadecanolide, 5-icosanolide, 6-decanolide, 6-dodecanolide, 8-hexadecanolide, 10-hexadecanolide, 12-hexadecanolide, bovolide, dihydrobovolide, 2-decen-5-olide, 4-decen-5-olide, 5-decen-5-olide, 6-decen-6-olide, cis-7-decen-5-olide, 3-isopropyl-2-penten-5-olide, 3-methyl-2-buten-4-olide, and 2,3-dimethyl-2-penten-4-olide, and 3-hydroxy-4,5-dimethyl-2(5H)-furanone.
As the macrocyclic ketone used in the present invention, any compound represented by the following general formula (4) may be used: 
wherein R5 is hydrogen or an alkyl or alkylene group having 1 to 4 carbon atoms, R6 is a carbon chain having 7 to 17 carbon atoms which is saturated or unsaturated by including one or two carbon-carbon double bonds in any positions, where an alkyl or alkylene group having 1 to 4 carbon atoms may be linked to any position as a side chain, R7 is hydrogen or an alkyl group or an alkylene group having 1 to 4 carbon atoms, and the dashed line represents a single bond or a double bond. The industrial production methods for the macrocyclic ketones have been established, and the macrocyclic ketones of the present invention may be produced by the known methods. However, these compounds have already been mass-produced as fragrance materials. For example, 5-cyclohexadecen-1-one, 8-cyclohexadecen-1-one, 3-methylcyclopentadecanone, and 9-cycloheptadecen-1-one, which are easily obtainable as high-purity products, are most preferable.
Furthermore, as the macrocyclic diester used in the present invention, any compound represented by the following general formula (5) may be used: 
wherein R8 is a carbon chain having 2 to 10 carbon atoms which is saturated or unsaturated by including at least one carbon-carbon double bond in any position, where an alkyl or alkylene group having 1 to 4 carbon atoms may be linked to any position; and R9 is a carbon chain having 8 to 20 carbon atoms which is saturated or unsaturated by including at least one carbon-carbon double bond in any position. The industrial production methods for the macrocyclic diesters have been established, and the macrocyclic diesters used in the present invention may be produced by the known methods. However, these compounds have already been mass-produced as fragrance materials, and high-purity products are easily obtainable. Most preferred examples of macrocyclic diesters include ethylene dodecanedioate, ethylene tridecanedioate, ethylene tetradecanedioate, ethylene pentadecanedioate, ethylene hexadecanedioate, ethylene heptadecanedioate, ethylene octadecanedioate, ethylene nonadecanedioate, ethylene eicosanedioate, isopropylene dodecanedioate, isopropylene tridecanedioate, isopropylene tetradecanedioate, isopropylene pentadecanedioate, isopropylene hexadecanedioate, isopropylene heptadecanedioate, isopropylene octadecanedioate, isopropylene nonadecanedioate, isopropylene eicosanedioate, propylene dodecanedioate, propylene tridecanedioate, propylene tetradecanedioate, propylene pentadecanedioate, propylene hexadecanedioate, propylene heptadecanedioate, propylene octadecanedioate, propylene nonadecanedioate, propylene eicosanedioate, butylene dodecanedioate, butylene tridecanedioate, butylene tetradecanedioate, butylene pentadecanedioate, butylene hexadecanedioate, butylene heptadecanedioate, butylene octadecanedioate, butylene nonadecanedioate, and butylene eicosanedioate.
With respect to the compounds used as anticancer agents in the present invention, for example, if they have optical isomerism, racemic mixtures may be acceptable, and it is possible to select the ratio thereof arbitrarily up to an optical purity of 100%. For example, if the compounds have geometrical isomerism, it is possible to select the ratio thereof arbitrarily from 0 to 100%.
Examples of the bases constituting the salts of the xcfx89-hydroxy fatty acids or hydroxy oxo-fatty acids used in the present invention include, but are not limited to, alkaline metals, such as sodium and potassium, and alkaline-earth metals, such as calcium and magnesium, and examples of the organic bases constituting the salts include, but are not limited to, trimethylamine, triethylamine, pyridine, ethanolamine, diethanolamine, and dicyclohexylamine.
Examples of the esters of the xcfx89-hydroxy fatty acids or hydroxy oxo-fatty acids used in the present invention include, but are not limited to, esters with monools, such as methanol, ethanol, 1-propanol; esters with diols, such as ethylene glycol and propylene glycol; esters with triols, such as glycerol; and esters with sugars, such as glucose and sucrose, but are not limited thereto.
With respect to the xcfx89-hydroxy fatty acids and salts or esters thereof, hydroxy oxo-fatty acids and salts or esters thereof, lactones, macrocyclic ketones, and macrocyclic diesters, since the cytotoxicity is significantly low compared to the traditional anticancer agents, it is possible to administer them to mammals including humans orally or parenterally, for example, by inhalation, percutaneous absorption, nasal absorption, rectal absorption, instillation, intravascular injection, and subcutaneous injection.
The anticancer agents of the present invention may be formulated in any dosage form, for example, as liquid drugs, orally administered drugs, tablets, powders, suppositories, external preparations, bath preparations, pastes, plasters, eye drops, intravenously injectable solutions, powdered drug, granules, sugar-coated tablets, capsules, pills, suspensions, ampoules, parenteral solutions, and inhalants, by mixing with various types of known carriers which are pharmacologically acceptable liquids or solids and by adding thereto, as necessary, stabilizers, colorants, corrigents, flavoring substances, diluting agents, solvents, surface active agents, emulsifiers, suspending agents, dispersants, preservatives, solubilizing agents, isotonizing agents, buffer agents, soothing agents, moisturizing agents, binders, coating materials, glazing agents, disintegrating agents, etc.
Additionally, among the compounds used in the present invention, for example, 15-pentadecanolide is known to have a superior property as a transdermal absorption promoting agent (e.g., as disclosed in Japanese Patent No. 2583777 and JP-A-4-275217). Therefore, when an external preparation for skin or plaster is formulated by mixing the 15-pentadecanolide with other active ingredients and clinically used, the 15-pentadecanolide by itself acts as an anticancer agent, and it is also expected that the rate of transdermal absorption of other active ingredients be increased. From this viewpoint, the present invention can also provide breakthrough anticancer agents which are not conventionally available.
The content of the anticancer agents of the present invention, i.e., at least one compound selected from the group consisting of xcfx89-hydroxy fatty acids and salts or esters thereof, hydroxy oxo-fatty acids and salts or esters thereof, lactones, macrocyclic ketones, and macrocyclic diesters, is preferably 0.001 to 100% by weight in a preparation or composition.
With respect to at least one compound selected from the group consisting of xcfx89-hydroxy fatty acids and salts or esters thereof, hydroxy oxo-fatty acids and salts or esters thereof, lactones, macrocyclic ketones, and macrocyclic diesters used in the present invention, although it depends on symptoms, age, gender, body weight, dosage form, or administration mode, the effective dose per day for an adult is usually 0.001 to 10,000 mg/kg, and preferably 1 to 100 mg/kg in the case of oral administration, suppositories, external preparations, and the like, and the effective dose per day for an adult is usually 0.01 to 200 mg/kg, and preferably 0.25 to 100 mg/kg in the case of intravenous injection and drip infusion, in a single or divided dose.
The anticancer agents of the present invention are effective in treating mammals in general having tumors, and are drugs which are remarkably effective in prolonging lives of the tumor bearing animals and in inhibiting metastasis of cancer.
Examples of diseases to which the anticancer agents of the present invention are targeted include various benign and malignant tumors, such as malignant melanoma, malignant lymphoma, pharyngeal cancer, laryngeal cancer, gastric cancer, Kaposi""s sarcoma, liver cancer, myosarcoma, colonic cancer, angioma, myeloma, thyroid cancer, testicular tumor, pancreatic cancer, cancer of the digestive organs, esophageal cancer, large bowel cancer, cancer of the upper jaw, lingual cancer, labial cancer, oral cancer, gallbladder cancer, bile duct cancer, biliary tract cancer, rectal cancer, mammary cancer, ureteral tumor, sarcoma, osteogenic sarcoma, brain tumor, leukemia, lung cancer, neuroblastoma, polycythemia vera, bladder tumor, ovarian cancer, uterine cancer, prostate cancer, myosarcoma, skin cancer, basal cell cancer, skin appendage cancer, metastatic skin cancer, and skin melanoma.
It is possible to enhance the anticancer effect by combining at least one compound selected from the group consisting of xcfx89-hydroxy fatty acids and salts or esters thereof, hydroxy oxo-fatty acids and salts or esters thereof, lactones, macrocyclic ketones, and macrocyclic diesters as the active ingredient in the anticancer agents of the present invention with a specific known antitumor agent. Examples of antitumor agents which show such a synergistic effect include at least one agent selected from the group consisting of angiostatic steroid coexistent with heparin, aceglatone, actinomycin D, adriamycin, ifosfamide, Estracyt (registered trade name), etoposide, enocitabine, epitiostanol, aclarubicin hydrochloride, ancitabine hydrochloride, daunorubicin hydrochloride, doxorubicin hydrochloride, nimustine hydrochloride, procarbazine hydrochloride, carboquone, carboplatin, carmofur, tamoxifen citrate, Krestin (registered trade name), chromomycin A3, antitumor polysaccharides, antitumor platelet factors, cyclophosphamide, cisplatin, Schizophyllan, cytarabine, dacarbazine, thioinosine, thiotepa, tegafur, Nitromin (registered trade name), neocarzinostatin, OK-432, vincristine, vindesine, bleomycin, fluorouracil, furtulon, broxuridine, Protecton (registered trade name), busulfan, pepleomycin, honvan, Mitomycin C (registered trade name), methotrexate, peplomycin, VePesid (registered trade name), Bestatin (registered trade name), interferon-xcex2, mepitiostane, mitobronitol, mercaptopurine, merphalan, laminin peptides, vincristine sulfate, vindesine sulfate, vinblastine sulfate, bleomycin sulfate, peplomycin sulfate, lentinan, MDS Kowa 3000 (registered trade name), UFT (registered trade name), and various types of interferons.
When another antitumor agents and at least one compound selected from the group consisting of xcfx89-hydroxy fatty acids and salts or esters thereof, hydroxy oxo-fatty acids and salts or esters thereof, lactones, macrocyclic ketones, and macrocyclic diesters used in the present invention are combined, the dosage of the compound of the present invention is selected from the range for the independent dosage described above, and the dosage of the other antitumor agents to be combined is also selected from the range for the independent dosage (concentration) clinically administered. The dosage may be adjusted appropriately.
When the existing antitumor agents are administered to an organism and in the case of a human body, various side effects may be generated, for example, leukopenia, thrombocytopenia, loss of appetite, vomiting, stomatitis, diarrhea, exanthema, alopecia, chromatosis, fever, headache, liver function failure, proteinuria, and edema. However, if the existing antitumor agents are combined with at least one compound selected from the group consisting of xcfx89-hydroxy fatty acids and salts or esters thereof, hydroxy oxo-fatty acids and salts or esters thereof, lactones, macrocyclic ketones, and macrocyclic diesters, which are the active ingredients of the present invention, since a small dose of the compound used in the present invention has the anticancer effect, the content of the existing antitumor agents can be decreased, resulting in a reduction in the side effects of the existing antitumor agents.
In another aspect, the anticancer agents of the present invention can be added to a toiletry article. Examples of the toiletry articles to which the anticancer agents of the present invention can be added are perfume, eau de cologne, lotion, milky lotion, cream, gel, nourishing lotion, pack agents, after-shave lotion, foundation, face powder, lip sticks, rouge, nail treatments, shampoos, rinses, hair growth agents, hair-dyeing agents, soaps, cleansing lotion, sun care products, deodorants, toothpaste, and mouthwash.
The content of the anticancer agents of the present invention is preferably 0.001 to 10.0% by mass of the toiletry article.
It is also possible to add the anticancer agents of the present invention to the toiletry articles described above in combination with other medicinal properties.
In another aspect, the anticancer agents of the present invention can be added to a food. Examples of the foods to which the anticancer agents of the present invention can be added include drinks, such as soft drinks, fruit drinks, alcoholic beverages, milk beverages, and luxury drinks; confectionery, such as chocolates, cookies, chewing gum, candies, snacks, and jelly; cereals; seasoning; spices; edible oil; cooked food; processed agricultural products; processed meat products; processed marine products; hospital diet; and fluid diet. The content of the anticancer agents of the present invention is preferably 0.001 to 10.0% by mass of the food.
It is also possible to add the anticancer agents of the present invention to the foods described above in combination with other medicinal properties.
By adding the anticancer agents of the present invention to the toiletry articles and the foods, the effect of preventing cancer and the effect of preventing the recurrence of cancer, in particular, can be expected.